Psoriasis is a chronic inflammatory skin disease which causes disfiguring skin eruptions in children and adults. Immunohistologic studies of psoriatic plaques show hyperplastic proliferation of epidermal keratinocytes juxtaposed to activated T lymphocytes and antigen presenting cells including epidermal Langerhans cells and dermal dendritic cells. Multiple lines of evidence suggest that T lymphocytes are of primary importance in the pathogenesis of psoriasis and include studies showing that: potent T-cell immunosuppressive medications such as cyclosporin and FK506 (tacrolimus) cause regression of psoriasis which returns when the medication is discontinued. Interactions between pairs of T-cell co-stimulatory molecules and professional and tissue APC ligands in psoriatic skin are hypothesized to be important in the initiation and perpetuation of the chronic inflammatory changes observed during psoriasis. Interactions of T-cell surface molecules and their ligands expressed on skin immunocytes include but are not limited to LFA-1 (CD11a/CD18)/ICAM-1, and CD28/BB1. In vitro adhesion assays have demonstrated adhesive interactions between the T-cell surface molecule CD6, and CD6 cell surface ligands expressed in gamma-interferon activated keratinocytes. CD6 has previously been shown to be important during T cell responses to nominal, allo and self antigen. We now hypothesize that interactions of T cell CD6 and CD6 ligands in skin immunocytes may represent a novel pathway which is important in initiation and/or perpetuation of the inflammatory response seen in psoriasis. In order to determine the role of CD6/CD6 ligand interactions in psoriatic skin, this application proposes funding to characterize the expression of CD6 and CD6 ligands expressed in psoriatic skin, and to biochemically identify these skin immunocyte CD6 ligands.